A growing proportion of children and adults take medication regularly, yet relatively few drugs have undergone significant post-marketing surveillance for adverse effects, including elevated cancer rates. The main objective of our originally funded proposal was to identify commonly prescribed drugs that are associated with lower or higher rates of cancer and examine whether these associations deserved further study. The study was conducted within Kaiser Permanente of Northern California (KPNC), a prepaid, integrated health plan with over 3.2 million currently active members. We conducted surveillance analyses (i.e., hypothesis generating) of the 230 most commonly prescribed drugs (at least 30,000 recipients from 1994-2003) with a special focus on the 115 drugs not examined in our previous program of surveillance of drugs for carcinogenicity, as well as several more in-depth analyses of drug-cancer associations (i.e., hypothesis testing). In this Renewal application, we are requesting funding to continue our surveillance of commonly prescribed drugs for carcinogenicity, as well as to examine selected drug-cancer associations of potential importance. This Renewal application builds on a drug surveillance program conducted within KPNC since the late 1970s. Specifically, we propose to: 1) Continue surveillance of commonly used prescription drugs for possible carcinogenic effects (i.e., hypothesis generation) among KPNC members with computer-stored pharmacy records since 1994, and 2) Conduct studies of selected drug-cancer associations found in the above screening analyses or from reports of human or animal studies (i.e., hypothesis testing). During the calendar period of the Renewal over two million of our members will be prescribed one or more drugs and approximately 18,000 members will be diagnosed with cancer per year for a total of approximately 320,000 cancers diagnosed among members during the period of study (1994-2013). The KPNC membership and databases continue to provide a unique resource for cost-efficient surveillance of a large number of prescription drugs for possible carcinogenic effects and for more in-depth studies of specific drug-cancer associations. The membership is large, stable, ethnically diverse, and receives virtually all of its health care from the pre-paid, integrated medical care program. Hard copy and electronic medical records are available with information on prescribed medications, cancer diagnoses, laboratory tests, and outpatient visits and hospitalizations. PUBLIC HEALTH RELEVANCE: New drug development continues at a rapid pace and a growing proportion of children and adults in the US take one or more medications on a regular basis. Yet despite growing public and scientific concern about potential health risks, there has been relatively little surveillance of commonly prescribed drugs for adverse effects, including elevated cancer rates. The Kaiser Permanente of Northern California surveillance program has been designed to detect signals of potential cancer risk associated with commonly prescribed drugs and to conduct more in-depth investigations of specific medications. Our program provides a valuable mechanism to identify early signs of possible carcinogenic effects of the most commonly used medications or reassurance as to their safety in this regard.